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Human brain processes underlying real-life social interaction in everyday situations have been difficult to study and have, until now, remained largely unknown. Here, we investigated whether electrocorticography (ECoG) recorded for pre-neurosurgical diagnostics during the daily hospital life of epilepsy patients could provide a way to elucidate the neural correlates of non-experimental social interaction. We identified time periods in which patients were involved in conversations with either their respective life partners (Condition 1; C1) or attending physicians (Condition 2; C2). These two conditions can be expected to differentially involve subfunctions of social interaction which have been associated with activity in the anterior temporal lobe (ATL), including the temporal pole (TP). Therefore, we specifically focused on ECoG recordings from this brain region and investigated spectral power modulations in the alpha (8–12 Hz) and theta (3–5 Hz) frequency ranges, which have been previously assumed to play an important role in the processing of social interaction. We hypothesized that brain activity in this region might be sensitive to differences in the two interaction situations and tested whether these differences can be detected by single-trial decoding. Condition-specific effects in both theta and alpha bands were observed: the left and right TP exclusively showed increased power in C1 compared to C2, whereas more posterior parts of the ATL exhibited similar (C1 > C2) and also contrary (C2 > C1) effects. Single-trial decoding accuracies for classification of these effects were highly above chance. Our findings demonstrate that it is possible to study the neural correlates of human social interaction in non-experimental conditions. Decoding the identity of the communication partner and adjusting the speech output accordingly may be useful in the emerging field of brain-machine interfacing for restoration of expressive speech.